Anti-blepharitis compositions and their use

ABSTRACT

Compositions and methods for the prevention and treatment of blepharitis, where the compositions include verbascoside, oligopeptide-10, and sulfonated shale oil, and the preparation of such compositions.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional application under 35 U.S.C. §121 ofU.S. patent application Ser. No. 14/981,329 filed Dec. 28, 2015, nowU.S. Pat. No. 9,439,917, the disclosure of which is hereby incorporatedby reference.

TECHNICAL FIELD

The disclosure relates generally to cosmetic compositions, and morespecifically to cosmetic compositions useful for the treatment and/orprevention of blepharitis

BACKGROUND

Blepharitis refers to inflammation of the eyelid. It is a common oculardisorder affecting millions of Americans, and may result from any of acontinuum of inflammatory disease processes of the eyelid. Blepharitismay be divided anatomically into anterior and posterior blepharitis.Anterior blepharitis refers to inflammation around the eyelashes andfollicles, while posterior blepharitis involves the meibomian glands.The pathophysiology of blepharitis involves bacterial colonization ofthe eyelids, which in turn results in immune-mediated inflammatorydamage to the surrounding tissues.

Sufferers of blepharitis typically present with various complaintsincluding burning, watery eyes, foreign body sensation, red eyelids, redeyes, pain and blurry vision. A physical examination of patients withblepharitis can often show a loss of eyelashes, the plugging of themeibomian glands, and/or infection of the conjunctiva. Also, theirritation that blepharitis causes can often lead to dry eyes. If it issevere enough, blepharitis may even affect the cornea, causing marginalinfiltrates, marginal ulcers, and pannus formation.

Ophthalmologists often see female patients wearing heavy cosmetics thatalso complain of the symptoms of blepharitis. In such situations, eventhough the patients are advised to stop wearing the cosmetics theytypically refuse, in order to maintain their desired appearance.

What is needed are formulations that may be useful for treating orpreventing blepharitis, and in particular cosmetic formulations thathave anti-bacterial and anti-inflammatory properties.

SUMMARY

The present disclosure provides compositions useful for the preventionand/or treatment of blepharitis, methods for preventing or treatingblepharitis in a subject, and methods for preparing compositions usefulfor the prevention and/or treatment of blepharitis.

In some embodiments, the disclosure may provide compositions thatinclude verbascoside, oligopeptide-10, and sulfonated shale oil.

In some embodiments, the disclosure may provide methods for preventingor treating blepharitis in a subject, the methods including topicallyapplying an effective amount of a composition that includes verbascosidein a concentration of 1.0×10⁻⁴ to 1.0 percent by weight, oligopeptide-10in a concentration of 5.0×10⁻⁶ to 0.50 percent by weight, and sulfonatedshale oil in a concentration of 1.0×10⁻⁴ to 2.0 percent by weight.

In some embodiments, the disclosure may provide methods for preparingcompositions effective for treating or preventing blepharitis, themethods including preparing a concentrated mixture that includes 0.001to 10 weight percent verbascoside, 0.0001 to 0.5 weight percentoligopeptide-10, and 0.001 to 20 weight percent sulfonated shale oil;and then combining the concentrated mixture with one or morecosmetically acceptable excipients.

The features, functions, and advantages of the disclosure may beachieved independently in various embodiments, or may be combined in yetother embodiments, further details of which can be seen with referenceto the following description.

DETAILED DESCRIPTION

The present disclosure is directed to compositions that possessunexpected efficacy in treating or preventing the symptoms ofblepharitis. In particular, the present disclosure is directed tocompositions containing a combination of verbascoside, oligopeptide-10,and sulfonated shale oil. In some embodiments, these compositions areformulated as cosmetic compositions, which unlike traditional cosmetics,do not cause or exacerbate the symptoms associated with blepharitis.

Verbascoside is a naturally occurring phenylpropanoid glycoside (PPG)that is a water-soluble derivative of phenylpropanoid (PP), and has thechemical formula:

Verbascoside, also known as acteoside or kusaginin, exhibitsanti-inflammatory and anti-bacterial activity, and may be obtained byisolation or extraction from any of a variety of medicinal plants thatcontain the compound, for example in species of all the families of theLamiales order. In particular, verbascoside may be obtained from theleaves of the Buddleja cordata tree by drying, grinding, and extractingthe leaves with hexane and methanol. The methanolic portion of theextract may be evaporated to obtain a crude syrup that may be furthertreated to produce a verbascoside amorphous powder. Alternatively or inaddition, verbascoside may be purchased from a number of commercialsuppliers (SIGMA-ALDRICH, ADOOQ BIOSCIENCE, among others).

The commercially-available Oligopeptide-10 (made by HELIX BIOMEDIX anddistributed by GRANT INDUSTRIES, NJ) is a proprietary oligopeptidehaving anti-microbial properties (see U.S. Pat. No. 7,381,704, herebyincorporated by reference). Oligopeptide 10 may be stable over a broadrange of temperatures and pH values.

Shale oil refers to oil that is extracted from fissures in shale,typically by pyrolysis or thermal extraction. Shale oils are useful asanti-inflammatory, anti-bacterial, and/or antimycotic agents whenapplied topically, and sulfonation of shale oil may render it partiallyor completely water-soluble. Although any sulfonated shale oil suitablefor topical use is appropriate for the present compositions, palesulfonate shale oil (or PSSO) may be particularly advantageous.Appropriate sulfonated shale oils for the purposes of the presentdisclosure may be obtained commercially from ICHTHYOL GESELLSCHAFT(Hamburg, Germany), in particular a dark sulfonated shale oil(ICHTHAMMOL®) and a light-colored pale sulfonated shale oil (ICHTHYOL®PALE).

Although each of verbascoside, oligopeptide-10, and sulfonated shale oilpossess anti-inflammatory properties, the combination of all three in asingle composition confers upon that composition beneficialanti-inflammatory and anti-bacterial properties that are greater thanthat of any individual component. That is, the combination exhibits asynergistic effect, where the joint action of the three components whencombined is greater than the sum of their individual effects. This isparticularly true with respect to the treatment or prevention ofblepharitis, where the application of all three components providesimproved blepharitis prevention and treatment when compared to theresults of the administration of verbascoside, sulfonated shale oil, oroligopeptide-10 alone.

The verbascoside, oligopeptide-10, and sulfonated shale oil may beincorporated into the compositions of the present disclosure in anytherapeutically effective ratio or concentration. In one embodiment, thecompositions of the present disclosure include verbascoside in aconcentration of 1.0×10⁻⁴ to 1.0 percent by weight; includeoligopeptide-10 in a concentration of 5.0×10⁻⁶ to 0.50 percent byweight; and include sulfonated shale oil in a concentration of 1.0×10⁻⁴to 2.0 percent by weight.

The verbascoside, oligopeptide-10, and sulfonated shale oil may beincorporated into the compositions of the present disclosure in anysuitable form. In one embodiment of the present compositions, one ormore of the verbascoside, oligopeptide-10, and sulfonated shale oilcomponents may be present in the composition in an encapsulated form,that is coated by or enclosed within another substance in order toregulate the release of the free components over time, or to protect andstabilize the components with respect to environmental conditions.Various methods of encapsulation of compositions, such as cosmeticcompositions, are well known.

Where one or more components of the present compositions areencapsulated, the encapsulated components may be configured to bereleased immediately, released over time, or a mixture of immediate- andsustained-release encapsulations. Alternatively, or in addition,encapsulation of one or more components may be used to stabilize thecomponents with respect to exposure to oxygen, light, heat, or otheradverse conditions. For example, one or more components may beencapsulated in such a way that the free component is released at bodytemperature, but stabilized at less than body temperatures.

Complex S

In an illustrative method of preparing the compositions of the presentdisclosure, the verbascoside, oligopeptide-10, and sulfonated shale oilcomponents, optionally in combination with one or more additionalcomponents, may be precombined to create a relatively concentratedmixture herein referred to as Complex S. The Complex S mixture may thenbe incorporated into compositions of the present disclosure in thedesired concentration. In one embodiment of the present disclosure,Complex S is incorporated into compositions of the present disclosure toa concentration of about 0.0001% to 5% by weight. Alternatively, thedesired active ingredients of Complex may be added individually or insubcombinations, provided that the active ingredients are present incombination in the final composition.

In addition to verbascoside, oligopeptide-10, and sulfonated shale oil,the Complex S mixture may include one or more additional activeingredients. By active ingredient is meant a substance, extract, orcompound that exhibits one or more of anti-bacterial, anti-microbial,and anti-inflammatory activity, or that enhances the anti-bacterial,anti-microbial, or anti-inflammatory activity of another ingredient,particularly when applied topically. Selected active ingredients thatmay be combined in Complex S include, but are not limited to, neem oil,turmeric extract, willowbark extract, Euphreisia officinalis extract,Cipadessa baccifera extract, black seed oil, and anise extract, amongothers. Representative and exemplary ingredients for the Complex Smixture as an aqueous composition, and a range of ingredientconcentrations, are provided in Table 1.

TABLE 1 Exemplary Ingredients of Complex S Ingredients % W/WVerbascoside 0.001-10    Oligopeptide-10 0.0001-0.5    Shale Oil0.001-20    Neem Oil  0-20 Tumeric Extract  0-10 Willowbark Extract 0-15 Euphrasia officinalis Extract  0-25 Black Seed Oil   0-1.0 AniseExtract   0-1.0 Dionized water qs to 100%Compositions

The Complex S mixture may be used to prepare a variety of compositionsfor topical application useful for treating and/or preventing skinirritations caused by bacterial infection. In one aspect of the presentdisclosure, the compositions of the present disclosure are cosmeticcompositions useful for the prevention and/or treatment of blepharitis.

In addition to active ingredients, as set out above, the compositions ofthe present disclosure may additionally include one or more cosmeticexcipients. A cosmetic excipient, as used herein, may be any natural orsynthetic substance formulated alongside the active ingredient of acomposition that is included for the purpose of, for example, long-termstabilization, bulking up solid compositions, diluting thosecompositions that contain potent active ingredients, facilitatingflowability, and reducing aggregation, among other purposes.

Selected cosmetic excipients may include solvents, waxes, oils, lipids,fatty alcohols, colorants, flavoring, fragrances, sequestrants,humectants, thickening agents, emulsifiers, emollients, adsorbingagents, preservatives, vitamins, antioxidants, pH modifiers, texturizingagents, silicas, and other ingredients usually used in cosmeticproducts, or combinations thereof.

When present, the organic solvents of the present compositions mayinclude any organic solvent that is suitable for use in cosmeticproducts, such as aliphatic hydrocarbons having 12-22 carbon atoms,including isoparaffins like isohexane and isododecane; or diols, such as1,3-butylene glycol.

When present, the waxes of the present compositions may include one ormore of candelilla wax, carnauba wax, beeswax, ceresine,microcrystalline wax, paraffin wax, silicon wax, and polyethylene wax,among others. Alternatively, or in addition, the present compositionsmay include one or more silicones or silicone derivatives, such ascyclomethicone, and dimethicone, among others.

When present, suitable colorants may include for example iron oxides,chromium oxide and/or hydroxide, blue and pink ultramarine, manganeseviolet, titanium dioxide, pearlescent pigments based on mica or bismuthoxychloride substrates, carmin, lakes and pigments based on organiccolorants, among others.

Additional suitable cosmetically acceptable excipients may includeglycerine, xanthan gum, talc, mica, kaolin, unmodified clays, zincoxide, calcium carbonate, magnesium carbonate phosphate, calciumbisulfate, starch and its derivatives, nylon, polyethylene, and acrylic(co)polymers, among others. Such excipients may comprise the balance ofthe total composition as further illustrated by the examples providedbelow. The individual concentrations of the components of the disclosedcompositions may depend upon the type of composition being produced, andits intended use. For example, the composition may be formulated to be aliquid, semiliquid, paste, or cake. Individual concentrations ofsuitable excipients are listed in the examples, but these individualconcentrations may be modified in either direction, to a higher or lowerpercentage, as needed.

The cosmetic compositions of the present disclosure may be formulated tofunction as lotions, creams, eye pencils, eye shadows, hydroalcoholicliquids or sprays, cosmetic primers, cosmetic sera, mascaras, eyeliners,and single phase liquids or sprays, among others. These cosmeticcompositions can be applied topically on any exposed skin surface thatcould be affected by blepharitis including, but not limited to, eyelidsand the areas surrounding each of the eyes.

Prevention/Treatment of Blepharitis

The compositions of the present disclosure may be highly useful forpreventing and/or treating blepharitis in a subject. That is, thecompositions may be useful for preventing blepharitis in a subject thatdoes not yet manifest the symptoms of blepharitis, and may beadditionally and advantageously useful for the treatment of blepharitisin a subject already suffering from that condition.

The prevention or treatment of blepharitis in a subject may include amethod of topically applying a therapeutically effective amount of acomposition comprising verbascoside, oligopeptide-10, and sulfonatedshale oil to the subject. Topically applying the composition may includetopically applying the composition to an affected skin area of thesubject. In one aspect of the present disclosure, the composition may bea cosmetic composition.

The composition may be effective for preventing and/or treatingblepharitis where verbascoside is present in the composition in aconcentration of 1.0×10⁻⁴ to 1.0 percent by weight; oligopeptide-10 ispresent in the composition in a concentration of 5.0×10⁻⁶ to 0.50percent by weight; and sulfonated shale oil is present in thecomposition in a concentration of 1.0×10⁻⁴ to 2.0 percent by weight.

The application of the compositions of the present disclosure may behelpful for both preventing the presence of blepharitis and treating theseverity of blepharitis. In particular, application of the presentcompositions may help alleviate one or more symptoms of blepharitis,resulting in for example a reduction of sebum production, a reduction ofbacterial growth, and the unclogging of pores in the affected area.

Preparation of the Compositions

The compositions of the present disclosure may be prepared in anyconvenient fashion, but may conveniently be prepared by firstformulating a relatively more concentrated Complex S mixture, which mayoptionally include one or more additional active ingredients, and thencombining an aliquot of the Complex S mixture with the desired cosmeticexcipients to form a composition having the desired appearance,consistency, fragrance, and color.

Although the preparation of selected embodiments of the compositions ofthe present disclosure are described in the examples below, theseexamples are provided only to illustrate selected aspects of thedisclosure, and are not intended to limit the scope of the disclosure,which is defined by the claims appended hereto.

EXAMPLES

The abbreviation “qs” stands for “quantity sufficient,” and may refer toan amount necessary to confer the desired effect (as in the case offragrances or preservatives), or an amount necessary for the sum of theingredients concentrations to equal 100% w/w (as in the case ofdeionized water).

Example 1. Preparation of Complex S

Although suitable compositions may be prepared by using similarconcentrations of the various components of Complex S individually, orin subcombinations, it may be convenient to prepare an initial Complex Smixture, and then to use a portion of the Complex S mixture informulating each desired composition.

An illustrative Complex S mixture is described below in Table 2:

TABLE 2 Illustrative Complex S Formulation Ingredients % W/WVerbascoside 10.00 Oligopeptide-10 0.50 Shale Oil 20.00 Neem Oil 20.00Turmeric Extract 10.00 Willowbark Extract 15.00 Euphrasia officinalisExtract (in H₂O) qs to 100 Black Seed Oil 1.00 Anise Extract 1.00The Complex S formulation may be prepared as an aqueous solution. In oneaspect of the present disclosure, the Euphrasia officinalis extract isprovided as a solution in deionized water, and an amount of Euphrasiaofficinalis is used sufficient to obtain a desired concentration of theComplex S components.

The concentrations provided for the above illustrative Complex S mixtureare suitable for incorporation in a cosmetic composition at aconcentration of Complex S of about 5% or less. Higher percentages, orthe use of more concentrated active ingredients, may remain effective atpreventing and/or treating blepharitis, but may be more likely to causeskin irritation.

Example 2 Preparation of an Oil-in-Water Lotion Formulation

Ingredient % (w/w) Phase A Deionized Water qs 1,3 Butylene Glycol 5.00Glycerine 3.00 Disodium EDTA 0.10 Xanthan Gum 0.30 Phase B Capric/caprictriglyceride 10.00 Octyl palmitate 5.00 Cetyl Alcohol 1.00 Dimethicone(350 cks) 1.00 PEG 100 Stearate 3.00 Stearyl alcohol 1.00 TocopherylAcetate 0.50 Salicylic Acid (as applicable)   0.1% to 20%   Phase CComplex S    0.0001 to 5%   Retinol or Retinol derivatives  0.01% to0.25% (as applicable) Phase D Fragrance qs Phase E Preservative qs

Phase A is prepared by adding the butylene glycol, glycerine, anddisodium EDTA to a mixture of the remaining ingredients in sufficientwater. The resulting combination is heated to 80° C.

Phase B is prepared by mixing the ingredients together and heating themixture to 80° C. Phase B is then added to Phase A while mixing. Theresulting mixture is cooled to 35° C. while being mixed. The ingredientsof Phases C, D, and E are then combined with the mixture to yield thedesired lotion formulation.

Example 3. Preparation of an Oil-in-Water Cream Formulation

Ingredient % (w/w) Phase A Deionized Water qs 1,3 Butylene Glycol 5.00Glycerine 3.00 Disodium EDTA 0.10 Xanthan Gum 0.30 Phase B Capric/caprictriglyceride 10.00 Octyl palmitate 5.00 Cetyl Alcohol 2.00 Stearylalcohol 1.00 Glyceryl Stearate 2.50 PEG 100 Stearate 3.00 TocopherylAcetate 0.50 Phase C Complex S    0.0001 to 5%   Retinol or Retinolderivatives  0.01% to 0.25% (as applicable) Phase D Fragrance qs Phase EPreservative qs Phase F Colorants qs

Phase A is prepared by adding the butylene glycol, glycerine anddisodium EDTA to water and the other ingredients of Phase A. Theresulting combination is then heated to 80° C.

Phase B is prepared by mixing the ingredients together and heating theresulting mixture to 80° C. Phase B is added to Phase A with mixing, andthe entire combined mixture is cooled to 35° C. while being mixed. Theingredients of phases D, E, and F are then added.

Example 4. Preparation of a Water-in-Oil Lotion Formulation

Ingredient % (w/w) Phase A Deionized Water qs 1,3 Butylene Glycol 5.00Glycerine 3.00 Disodium EDTA 0.10 Sodium Chloride 2.00 Phase BDimethicone and polysilicone-11 10.00 Octyl palmititate 5.00Dimethicone/and PEG/PPG 18/18 3.00 Dimethicone PEG-10 Dimethicone 3.00Beeswax 2.50 Tocopheryl Acetate 0.50 Phase C Complex S 0.0001% to 5%  Retinol or Retinol derivatives  0.01% to 0.25% (as applicable) Phase DFragrance qs Phase E Preservative qs Phase F Colorants qs

Phase A is prepared by adding the butylene glycol, glycerine, sodiumchloride, sodium borate, and disodium EDTA to a mixture of water and theremaining components. The resulting combination is then heated to 80° C.

Phase B is prepared by mixing the ingredients together and heating theresulting mixture to 80° C.

Phase B is added to Phase A with mixing. The entire resulting mixture isthen cooled to 35° C. while being mixed. The ingredients of Phases C, D,E, and F ingredients are then added.

Example 5 Preparation of a Composition Suitable for an Eye Pencil (A)

Ingredient % (w/w) Phase A Rhus Succedanea Fruit Wax qs HydrogenatedVegetable Oil 7.50 Hydrogenated Palm Kernel Glycerides 7.50 Stearic Acid5.00 Copernicia Cerifera (Carnauba) Wax 4.00 HydrogenatedCoco-Glycerides 3.00 Beeswax (Cera Alba) 2.00 Caprylic/CapricTriglyceride 2.00 Coco-Caprylate/Caprate 2.00 Tristearin 2.00Hydrogenated Palm Glycerides 2.00 Talc 1.00 Behenyl Behenate 0.50Preservative qs Tocopheryl Acetate <1% Aloe Barbadensis Leaf Extract0.50 Isopropyl Myristate 0.50 Isopropyl Palmitate 0.50 Iron Oxides CI77499 37.50  Ferric Ammonium Ferrocyanide CI 77510 2.00 Ultramarines CI77007 2.00 Carmine CI 75470 0.50 Complex S 0.0001% to 5%

All the components of Phase A are combined by mixing until uniform. Theresulting mixture is then formed into suitable shape for application toa user's eye.

Example 6. Preparation of a Composition Suitable for an Eye Pencil (B)

Ingredient % (w/w) Phase A Beeswax qs Coco Caprylate/Caprate 1.00 D&CBlack #2 10.00  Carnauba Wax (Copernicia 2.00 Cerifera (Carnauba) Wax)Euphorbia Cerifera (Candelilla) 3.00 Wax Microcrystalline Wax 4.00Polyethylene 2.00 Talc 7.00 Preservative qs Complex S 0.0001% to 5%Fragrance qs Colorants qs

All the components of Phase A are combined, and the resulting mixture isheated to 95° C. After heating, the mixture is mixed until uniform andthen cooled to room temperature. The resulting composition is thenformed into a suitable shape for application to a user's eye.

Example 7. Preparation of a Composition Suitable for an Eye Shadow

Ingredient % (w/w) Phase A Talc qs Zinc Stearate 7.00 Calcium Silicate0.10 Silica 5.00 Red Iron Oxide 0.30 Yellow Iron Oxide 1.00 Black IronOxide 0.10 Mica (and) Titanium Dioxide 15.00  Preservative qs Complex S0.0001% to 5% Coco Caprylate/Caprate 5.00 Isopropyl Isostearate 3.00Fragrance qs Colorants qs

The eye shadow is formed by mixing all components of Phase A togetheruntil uniform and forming the mixed components into a suitable shape forapplication to a user's eye.

Example 8. Preparation of a Composition Suitable for a HydroalcoholicLiquid or Spray

Ingredient % (w/w) Phase A Deionized Water qs Denatured Alcohol 20.00 1,3 Butylene Glycol 5.00 Glycerine 3.00 Phase B Complex S 0.0001% to 5%Phase C Fragrance qs Phase D Preservative qs Phase E Colorants qs

Phase A is prepared by combining all Phase A components. The Phase B, C,D, and E components are then mixed together, and the resulting mixtureis then combined with Phase A.

Example 9. Preparation of a Cosmetic Primer

Ingredient % (w/w) Phase A Deionized Water qs 1,3 Butylene Glycol 5.00Glycerine 3.00 Decyl glucoside 0.10 Polysorbate-20 0.10 Carbomer 0.20Hydroxy ethylcellulose 0.20 Phase B Dimethicone (and) Polysilicone-11(and) 15.00  Butylene Glycol (and) Water (and) Decyl Glucoside (SiW-066)Isododecane (and) Trimethylsiloxysilicate 10.00  (and) Water (and)Propanediol (and) Decyl Glucoside (SiW-MQIZ) Capric/Capric triglyceride1.00 Ammonium Acryloyldimethyltaurate/VP 0.50 Copolymer (Aristoflex AVC)Phase C Preservative qs Phase D Complex S 0.0001% to 5%

Phase A is prepared by combining all Phase A components. The Phase B, C,and D components are mixed together, and the resulting mixture is thencombined with Phase A.

Example 10. Preparation of a Mascara Formulation

Ingredient % (w/w) Phase A Deionized Water qs Hydroxyethylcellulose 0.75Black iron oxide 10.00 Phase B Glyceryl Stearate 4.00 Carnauba Wax(Copernicia Cerifera 5.00 (Carnauba) Wax) Stearic Acid 4.00 PropyleneGlycol Stearate 2.00 Beeswax 4.00 C18-36 Triglyceride 0.40 Paraffin Wax(Paraffin) 1.00 Phase D Acrylates Copolymer 10.00 Phase E Silica Beads(Silica) 2.00 Complex S 0.0001 to 5% DI Water 4.00

Phase A is prepared by all of the Phase A components, and then heatingthe combined mixture to 85° C. Phase B is prepared by mixing the Phase Bcomponents together, and heating the resulting mixture to 85-90° C.

While warm, Phase B is added to Phase A with mixing. The combinedmixture is then cooled to 35° C. with additional mixing. The Phase C, D,and E, components are then added.

Example 11. Preparation of a Waterproof Mascara Formulation ContainingIron Oxide

Ingredient % (w/w) Phase A Petroleum Distillates qs Tall Oil Glycerides5.00 Black iron oxide 10.00 Ozokerite Wax (Ozokerite) 5.00 Carnauba Wax(Copernicia Cerifera 6.00 (Carnauba) Wax) Ethylcellulose 0.60Distinctive Gel ID (Quaternium-90 15.00 Bentonite (and) Isododecane(and) Propylene Carbonate Beeswax 2.00 Kaolin 5.00 Preservative qsSilica 0.30 Complex S 0.0001% to 5%

Phase A is prepared by combining all Phase A components and heating theresulting mixture to 95° C. Phase A is mixed until uniform, while hot,then cooled to room temperature and formed into a suitable shape forapplication to a user's eye.

Example 12. Preparation of an Eyeliner Formulation Containing Iron Oxide

Ingredient % (w/w) Phase A DI Water qs PVP 3.00 Black iron oxide 8.00Polyester - 5 5.00 Preservative qs Acrylates Copolymer 5.00 Complex S0.0001% to 5% Fragrance qs Colorants qs

Phase A is prepared by combining all Phase A components and heating theresulting mixture to 85° C. The components are mixed while hot untiluniform, then cooled to room temperature and formed into a suitableshape for application to a user's eye.

Example 13. Preparation of a Mascara Formulation Containing Iron Oxide

Ingredient % (w/w) Phase A Deionized Water qs Hydroxyethylcellulose 0.75Black iron oxide 10.00 Tromethamine 40% 5.69 Preservative qs Polyester -5 5.00 Phase B Glyceryl Stearate 4.00 Carnauba Wax (Copernicia Cerifera5.00 (Carnauba) Wax) Stearic Acid 4.00 Propylene Glycol Stearate 2.00Beeswax 4.00 C18-36 Triglyceride 0.40 Paraffin Wax (Paraffin) 1.00Salicylic Acid (as applicable)   0.1% to 20% Phase D Acrylates Copolymer10.00 Phase E Silica 0.20 DI Water 4.00 Complex S 0.0001% to 5%

Phase A is prepared by combining all of the Phase A components andheating the combined mixture to 85° C. Next, the Phase B ingredients aremixed together and heated to 85-90° C. While warm, the Phase B mixtureis added to Phase A with mixing. While continuing to mix the combinedmixture, it is cooled to 35° C. The Phase C, D, and E components arethen added to the mixture.

Example 14. Preparation of a Single Phase Cosmetic Liquid or Spray

Ingredient % (w/w) Phase A Deionized Water qs 1,3 Butylene Glycol 5.00Glycerine 3.00 Complex S 0.0001% to 5% Phase B Preservative qs

Phase A is prepared by combining all Phase A ingredients. Theingredients are mixed until uniform, and then added to the Phase Bcomponent.

Example 20. Preparation of Makeup Remover Wipes

Ingredient % (w/w) Phase A Water qs Complex S 0.0001% to 5% Methylglucose sesquistearate 1.00 PEG 20 Methyl glucose sesquistearate 0.80Phase B Isohexadecane 10.00 Hexylene Glycol 7.00 Dimethicone 3.00Isopropyl palm itate 1.00 Trisiloxane 1.00 Tocopherol 0.20 Phase CPreservative qs

Phase A is prepared by combining all Phase A ingredients and mixinguntil the combination is uniform. Phase A is then combined with thePhase B and C ingredients and again mixed until uniform. A quantity ofporous sheets suitable for use as makeup remover wipes are thenimpregnated with the resulting mixture.

Although the compositions and methods of the present disclosure havebeen shown and described with reference to the foregoing operationalprinciples and preferred embodiments, it will be apparent to thoseskilled in the art that various changes in form and detail may be madewithout departing from the spirit and scope of the disclosure. Thepresent invention is intended to embrace all such alternatives,modifications and variances that fall within the scope of the appendedclaims.

It is believed that the disclosure set forth above may encompassmultiple distinct inventions with independent utility. While each ofthese inventions has been disclosed in its preferred form, the specificembodiments thereof as disclosed and illustrated herein are not to beconsidered in a limiting sense as numerous variations are possible. Thesubject matter of the inventions includes all novel and non-obviouscombinations and subcombinations of the various elements, features,functions and/or properties disclosed herein. Similarly, where theclaims recite “a” or “a first” element or the equivalent thereof, suchclaims should be understood to include incorporation of one or more suchelements, neither requiring nor excluding two or more such elements.

Inventions embodied in various combinations and subcombinations offeatures, functions, elements, and/or properties may be claimed throughpresentation of new claims in a related application. Such new claims,whether they are directed to a different invention or directed to thesame invention, whether different, broader, narrower or equal in scopeto the original claims, are also regarded as included within the subjectmatter of the inventions of the present disclosure.

What is claimed is:
 1. A composition comprising verbascoside,oligopeptide-10, and sulfonated shale oil, wherein the verbascoside ispresent in the composition in a concentration of 1.0×10⁻⁴ to 1.0 percentby weight, the oligopeptide-10 is present in the composition in aconcentration of 5.0×10⁻⁶ to 0.50 percent by weight, and the sulfonatedshale oil is present in the composition in a concentration of 1.0×10⁻⁴to 2.0 percent by weight.
 2. The composition of claim 1, whereinverbascoside and shale oil are present in the composition in a ratio ofone part verbascoside to two parts shale oil by weight.
 3. Thecomposition of claim 1, wherein verbascoside and oligopeptide-10 arepresent in the composition in a ratio of 20 parts verbascoside to onepart oligopeptide-10 by weight.
 4. The composition of claim 1, furthercomprising one or more additional active ingredients selected from neemoil, turmeric extract, willowbark extract, Euphrasia officinalisextract, black seed oil, and anise extract.
 5. The composition of claim1, wherein verbascoside is present in the composition in a concentrationof about 0.5 percent by weight; oligopeptide-10 is present in thecomposition in a concentration of about 0.025 percent by weight; andsulfonated shale oil is present in a concentration of about 1.0 percentby weight.
 6. The composition of claim 1, wherein the composition is acosmetic composition, further comprising one or more cosmeticallyacceptable excipients.
 7. The composition of claim 6, wherein the one ormore excipients are selected from the group consisting of: solvents,sequestrants, humectants, thickening agents, emulsifiers, emollients,adsorbing agents, preservatives, fragrances, antioxidants, pH modifiers,texturizing agents, and combinations thereof.
 8. The composition ofclaim 6, wherein the composition is an eye pencil, an eye shadow, an eyeliner, a mascara, a cosmetic primer, or a cosmetic serum.
 9. Thecomposition of claim 1, wherein the composition is a lotion, a cream, ora liquid.
 10. The composition of claim 1, wherein the composition isdispersed on or in an absorbent substrate.
 11. A composition fortreating or preventing blepharitis, comprising: a precombinedconcentrated mixture of active ingredients including verbascoside,oligopeptide-10, and sulfonated shale oil; and at least one cosmeticexcipient; wherein the precombined concentrated mixture is present inthe composition in a concentration of 0.0001% to 5% by weight; andwherein the verbascoside is present in the composition in aconcentration of 1.0×10⁻⁴ to 1.0 percent by weight, the oligopeptide-10is present in the composition in a concentration of 5.0×10⁻⁶ to 0.50percent by weight, and the sulfonated shale oil is present in thecomposition in a concentration of 1.0×10⁻⁴ to 2.0 percent by weight. 12.The composition of claim 11, further comprising one or more additionalactive ingredients selected from neem oil, turmeric extract, willowbarkextract, Euphrasia officinalis extract, black seed oil, and aniseextract.
 13. The composition of claim 11, wherein verbascoside ispresent in the composition in a concentration of about 0.5 percent byweight; oligopeptide-10 is present in the composition in a concentrationof about 0.025 percent by weight; and sulfonated shale oil is present ina concentration of about 1.0 percent by weight.
 14. The composition ofclaim 11, wherein the composition is an eye pencil, an eye shadow, aneye liner, a mascara, a cosmetic primer, or a cosmetic serum.
 15. Thecomposition of claim 11, wherein the composition is a lotion, a cream,or a liquid.
 16. An eye makeup formulation, comprising: a precombinedconcentrated mixture of active ingredients for treating or preventingblepharitis, including verbascoside, oligopeptide-10, and sulfonatedshale oil collectively present in the formulation in a concentration of0.0001% to 5% by weight; a wax; and a colorant; wherein the verbascosideis present in the composition in a concentration of 1.0×10⁻⁴ to 1.0percent by weight, the oligopeptide-10 is present in the composition ina concentration of 5.0×10⁻⁶ to 0.50 percent by weight, and thesulfonated shale oil is present in the composition in a concentration of1.0×10⁻⁴ to 2.0 percent by weight.
 17. The formulation of claim 16,further comprising one or more additional active ingredients selectedfrom neem oil, turmeric extract, willowbark extract, Euphrasiaofficinalis extract, black seed oil, and anise extract.
 18. Theformulation of claim 16, wherein the colorant is an iron oxide.